| Autor: |
Greenhalgh, Kacy, Ramiro Garcia, Javier, Heinken, Ullmann, Pit, Bintener, Tamara Jean Rita, Pacheco, Maria, Baginska, joanna, Shah, Pranjul, Frachet Bour, Audrey, Halder, Rashi, Fritz, Joëlle, Sauter, Thomas, Thiele, Ines, Haan, Serge, Letellier, Elisabeth, Wilmes, Paul |
| Přispěvatelé: |
Fonds National de la Recherche - FnR [sponsor], Luxembourg Centre for Systems Biomedicine (LCSB) [research center] |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Cell Reports, 27, 1621–1632. Amsterdam, Netherlands: Elsevier (2019). |
| Popis: |
By modulating the human gut microbiome, prebiotics and probiotics (combinations of which are called synbiotics) may be used to treat diseases such as colorectal cancer (CRC). Methodological limitations have prevented determining the potential combina- torial mechanisms of action of such regimens. We expanded our HuMiX gut-on-a-chip model to co-culture CRC-derived epithelial cells with a model probiotic under a simulated prebiotic regimen, and we integrated the multi-omic results with in silico metabolic modeling. In contrast to individual prebi- otic or probiotic treatments, the synbiotic regimen caused downregulation of genes involved in procarci- nogenic pathways and drug resistance, and reduced levels of the oncometabolite lactate. Distinct ratios of organic and short-chain fatty acids were produced during the simulated regimens. Treatment of primary CRC-derived cells with a molecular cocktail reflecting the synbiotic regimen attenuated self-renewal ca- pacity. Our integrated approach demonstrates the potential of modeling for rationally formulating synbi- otics-based treatments in the future. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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